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1 Supporting Information Cells cultured on core-shell photonic crystal barcodes for drug screening Fanfan Fu, Luoran Shang, Fuyin Zheng, Zhuoyue Chen, Huan Wang, Jie Wang, Zhongze Gu, Yuanjin Zhao* State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing , China S-1
2 Supporting Figures Figure S1. Optical characterization of the core-shell PhC particles. (a) Optical image and (b) reflection spectrum of core-shell PhC particles with two reflection peaks. Scale bar is 200 µm. S-2
3 Figure S2. Result of the cell MTT assay based on the core-shell PhC particles with different GelMA shell layers. The HepG2 cells cultured on PhC particles (etching for 30 min) was the control experiment and the cellular activity of these cells were set as 100%. The number of replicates for each group was 10. Error bars represent standard deviations. S-3
4 Figure S3. CLSM images of the HepG2 tumor spheroids cultured on PhC core-shell particle: Penetrating percentage of these particles at 0 (a), 10 (b), 20 (c), 30 (d), 40 (e) and 50 (f) m distance from the bottom. Scale bar is 25 µm. The HCT-116 cells could also form similar 3D structure on the particles, while the NIH-3T3 fibroblasts cells only form monolayer on the particles. S-4
5 Figure S4. Reflection spectra of the core-shell PhC particles. (a) Reflection spectra of the core-shell PhC particles before and after cell adhesion; (b, c) distribution of reflection peak positions of the core-shell PhC particles (b) before and (c) after cell adhesion. As the cells only form monomer layer or several layers on the surfaces of the particles, the reflection of the barcode particles showed unobvious changes before and after cell adhesion. S-5
6 Figure S5. Images of different cells cultured on core-shell PhC particles. Hoechst fluorescent images, Calcein AM fluorescent images, and optical microscopy images of different cells cultured on the core-shell PhC particles: (a) HepG2 cells; (b) NIH-3T3 cells; (c) HCT-116 cells. Scale bar is 200 µm. S-6
7 Figure S6. Images of different cells with TF drug treatment. The Hoechst fluorescent images, Calcein AM fluorescent images, and optical microscopy images of the HCT-116 and NIH-3T3 co-culture systems before (a) and after (b) the TF drug treatment for 48 hours. The concentration of TF is 100 µm. Scale bar is 200 µm. S-7
8 Figure S7. The MTT assays of different cells with different drug treatment. Results of the cell MTT assays of the HCT-116 and NIH-3T3 co-culture systems (Figure S6) before and after the TF drug treatment for 48 hours: a) HCT-116 cells; b) NIH-3T3 cells. HCT-116 and NIH-3T3 cell-laden particles which were separately cultured without TF or 5-FU as control experiment and the cellular activity of these cells were set as 100%. The number of replicates for each group was 10. Error bars represent standard deviations. S-8
9 Figure S8. The optical microscopy images of the HCT-116 and HepG2 co-culture system before (a) and after (b) the TF drug treatment for 48 hours. (c) Reflection spectra of two kinds of core-shell PhC barcode particles. S-9
10 Figure S9. Images of HCT-116 and HepG2 co-culture systems with 5-FU drug treatment. The Hoechst fluorescent image (a), Calcein AM fluorescent image (b), and optical microscopy image (c) of the HCT-116 and HepG2 co-culture systems after the 5-FU drug treatment for 48 hours. The concentration of 5-FU is 100 µm. Scale bar is 200 µm. S-10
11 Figure S10. Images of HCT-116, HepG2 and NIH-3T3 co-culture systems with TF or 5-FU drug treatment. The Hoechst fluorescent images, Calcein AM fluorescent images, and optical microscopy images of the HCT-116, HepG2 and NIH-3T3 co-culture systems before (a), after the TF drug treatment (b), or after the 5-FU drug treatment (c) for 48 hours. The concentration of TF or 5-FU is 100 µm. Scale bar is 200 µm. S-11
12 Figure S11. Results of the cell MTT assays of the HepG2 and HepG2/NIH-3T3 co-culture systems before and after the TF or 5-FU drugs treatment for 48 hours. The concentration of TF or 5-FU was 200 µm. HepG2 cell-laden particles which were separately cultured without TF or 5-FU as control experiment and the cellular activity of these cells were set as 100%. The number of replicates for each group was 10. Error bars represent standard deviations. S-12
13 Figure S12. Cytochrome P450 (CYP3A4) activity in HepG2 cell-laden PhC core-shell particles; HCT-116 plus HepG2 cell spheroid co-culture system; and HCT-116, HepG2 plus NIH-3T3 co-culture systems. The activity of Cytochrome P450 (CYP3A4) in HepG2 cell-laden PhC core-shell particles was set as 100% as control. CYP3A4 enzyme activity was blocked with 10-6 M ketoconazole. The number of replicates for each group was 10. Error bars represent standard deviations. S-13
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